Is CFH p.Val609Asp (c.1826T>A) pathogenic?

CFH p.Val609Asp (c.1826T>A) is classified Uncertain significance in CFH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely pathogenic (0.7608); Absent from gnomAD v4.1; Associated with atypical hemolytic-uremic syndrome.

What condition is associated with CFH p.Val609Asp (c.1826T>A)?

CFH p.Val609Asp (c.1826T>A) is associated with atypical hemolytic-uremic syndrome (ClinVar).

How common is CFH p.Val609Asp (c.1826T>A) in the general population?

CFH p.Val609Asp (c.1826T>A) is absent from gnomAD v4.1 (gnomAD).

How is Atypical hemolytic uremic syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CFH p.Val609Asp (c.1826T>A)?

AlphaMissense predicts likely pathogenic (score 0.7608) — an in-silico prediction, not a clinical call.

CFH p.Val609Asp

c.1826T>A · VCV4291424

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7608 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

atypical hemolytic-uremic syndrome

Computational evidence

Protein change
AlphaMissense	0.7608	likely pathogenic
REVEL	0.359	indeterminate
SaProt	LLR -15.31	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.019	GERP -2.2
Regional constraint	o/e 1.01	unconstrained · MANE · 53 kb · p 0.76 · regional, not allelic
Overall
CADD	20.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CFH
Protein: p.Val609Asp
Coding: c.1826T>A
MANE Select: NM_000186
Type: single nucleotide variant
Location: chr1:196725250 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 609: the sushi 10 domain; a β-strand; a disulfide bond; a UniProt-annotated variant site (in ahus1)

Full CFH gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

atypical hemolytic-uremic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Atypical hemolytic uremic syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: All ages
Prevalence: 1-9 / 1 000 000 (United States)

Similar variants

CFH p.Val609Ile Uncertain significance ★★ ⚠ same residue
CFH p.Val609Ala Uncertain significance ★ ⚠ same residue
CFH c.1520-1G>A Pathogenic/Likely pathogenic ★★ same condition
CFH c.3493+1G>A Pathogenic/Likely pathogenic ★★ same condition
CFH c.619+1G>A Pathogenic/Likely pathogenic ★★ same condition
CFH p.Arg1215Leu Likely pathogenic ★★ ⚠ same condition
CFH p.Arg1215Ter Pathogenic/Likely pathogenic ★★ same condition
CFH p.Arg232Ter Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cfh-p-val609asp (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown